Maternal glucocorticoids increase endotoxin-induced lung inflammation in preterm lambs

• DOI: 10.1152/ajplung.00344.2002
• Publication Date: 2015-03-03T20:20:51Z
• Authors: Suhas G. Kallapur; Boris W. Kramer; Timothy J. M. Moss; John P. Newnham; Alan H. Jobe; Machiko Ikegami; Cindy J. Bachurski
• Keywords: 0301 basic medicine; Hydrocortisone; Interleukin-6; Neutrophils; Interleukin-8; Gene Expression; Drug Synergism; Pneumonia; Betamethasone; Monocytes; 3. Good health; Endotoxins; 03 medical and health sciences; Chorioamnionitis; Animals; Female; Lymphocyte Count; Lymphocytes; Acute-Phase Reaction; Bronchoalveolar Lavage Fluid; Glucocorticoids; Lung; Interleukin-1

Antenatal betamethasone (Beta) is widely used in women with asymptomatic chorioamnionitis at risk for preterm delivery, but its effects on fetal inflammation are unstudied. Groups of ewes at 109 ± 1 days of gestation received the following treatments: intra-amniotic (IA) saline (control), 0.5 mg/kg intramuscular Beta, 10 mg IA endotoxin (Endo), and Beta + 2 h later Endo (Beta + Endo). Beta suppressed Endo-induced lung inflammation at 1 day. However, compared with Endo 5 days after treatment, Beta + Endo lambs had increased alveolar neutrophils, proinflammatory cytokine mRNA expression, and serum amyloid A3 (SAA3) mRNA expression. IL-1β mRNA expression was localized to the inflammatory cells, whereas SAA3 mRNA expression was induced in the bronchial epithelium and the inflammatory cells. Compared with Endo, Beta + Endo lambs had increased lung inflammation but equivalent lung volumes 15 days after treatment. The late increase in inflammation in the Beta + Endo animals suggests that glucocorticoids impair the ability of the preterm lung to downregulate Endo-induced inflammation after fetal clearance of the glucocorticoids. These results have implications for lung inflammation and bronchopulmonary dysplasia in preterm infants exposed to chorioamnionitis and maternal glucocorticoids.